Septoplasty versus non-surgical management for deviated nasal septum: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of septoplasty versus non-surgical management for patients experiencing nasal obstruction due to deviated nasal septum (DNS). METHODS: We conducted a comprehensive search of PubMed, Scopus, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov, ICTRP, and ISRCTN for relevant RCTs. The primary outcomes included the Nasal Obstruction Symptom Evaluation (NOSE) scale, Sino-Nasal Outcome Test (SNOT-22), Peak Nasal Inspiratory Flow (PNIF), surgical complications, and quality of life. Data were synthesized using RevMan 5.4 and STATA 18, with effect estimates presented as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). The study protocol was registered with PROSPERO (ID: CRD42024538373). RESULTS: Our search identified 537 studies, of which 3 RCTs involving 721 participants met the inclusion criteria. The meta-analysis revealed that septoplasty significantly improved NOSE and SNOT-22 scores compared to non-surgical interventions at 6 and 12 months of follow-up, despite no notable differences at 3 months post-treatment. No significant difference was observed regarding nasal flow assessed by PNIF. The rate of complications was low, ranging from 0.31% (revision rate) to 4.12% (bleeding and infection rates). Additionally, our qualitative synthesis showed an improvement in the quality of life at 6 and 12 months in the septoplasty group compared with the non-surgical group. CONCLUSIONS: This systematic review and meta-analysis of 721 patients revealed the efficacy of septoplasty, with or without turbinate surgery, in improving nasal obstruction symptoms at 6 and 12 months. Additionally, septoplasty consists of a relatively low rate of complications such as bleeding, infection, and septal perforation. Furthermore, a low revision rate was found. Septoplasty improved the quality of life, especially after 6 and 12 months. However, our findings should be interpreted with caution, and further research is needed to consolidate our results.

Apical tubular complement activation and the loss of kidney function in proteinuric kidney diseases.

Many kidney diseases are associated with proteinuria. Since proteinuria is independently associated with kidney function loss, anti-proteinuric medication, often in combination with dietary salt restriction, comprises a major cornerstone in the prevention of progressive kidney failure. Nevertheless, complete remission of proteinuria is very difficult to achieve, and most patients with persistent proteinuria slowly progress toward kidney failure. It is well-recognized that proteinuria leads to kidney inflammation and fibrosis via various mechanisms. Among others, complement activation at the apical side of the proximal tubular epithelial cells is suggested to play a crucial role as a cause of progressive loss of kidney function. However, hitherto limited attention is given to the pathophysiological role of tubular complement activation relative to glomerular complement activation. This review aims to summarize the evidence for tubular epithelial complement activation in proteinuric kidney diseases in relation to loss of kidney function.

C4d, rather than C3d and C5b-9, is associated with graft loss in recurrent IgA deposition after kidney transplantation.

INTRODUCTION: Recurrent IgA deposition is common after kidney transplantation. However, it is difficult to define whether IgA deposition is innocuous or contributes to organ damage. Next, although complement is known to be involved in the pathogenesis of IgA nephropathy (IgAN), its involvement has not been studied systematically in kidney transplant recipients (KTR). METHODS: KTR with biopsy-proven native IgAN who underwent kidney biopsy after transplantation between 1995 and 2020 were included. Recurrent IgA deposition was defined as IgA deposit in the glomerulus. Staining of complement factors C4d, C3d, and C5b-9 were quantitatively evaluated using ImageScope. RESULTS: Sixty-seven KTR (85% male, 46±13 years old, 12 [6-24] months after transplantation, 58% with indication biopsy) were included in the analyses. Of them, 25 (37%) had recurrent IgA deposition. There were no clinical differences between KTR with and without recurrent IgA deposition. C3d and C5b-9 were always present in biopsies with IgA deposition, while C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTR developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition (Hazard ratio = 2.55, 95% confidence interval = 1.07-6.03, p = 0.034). CONCLUSIONS: Recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.

Molecular epidemiology of bovine theileriosis and genetic diversity of Theileria annulata in three governorates of Egypt.

Bovine theileriosis is a protozoan disease caused by the intracellular parasite (Theileria spp.) transmitted by ticks and it is considered one of the most significant parasitic diseases, potentially endangering Egyptian cattle herd industry. The present study was conducted for a molecular survey of bovine theileriosis and its associated risk factors (season variations, geographical locations, breeds, age, sex, tick infestation, and acaricide applications) in three Egyptian governorates, Beni-Suef, Al-Faiyum, and Al-Minya for a year extended from December 2021 to November 2022, in addition, genetic diversity of Theileria isolates. A total of 961 cattle were examined for Theileria infection clinically, microscopically, and by Polymerase Chain Reaction (PCR) using 18S rRNA gene for piroplasms DNA detection, Theileria genus-specific primers of the small subunit of rRNA gene, and Theileria annulata specific primers of the Tams-1 gene. The prevalence rate of bovine theileriosis was 9.26%, and 11.86% using Giemsa-stained blood smear and PCR, respectively. All positive samples screened by Theileria genus-specific primers were positive for T. annulata when screened by the specific primers. Based on molecular screening, season, cattle breeds and acaricide applications were considered risk factors for T. annulata infection, while locality, age, sex and tick infestation had insignificant effects with the occurrence of the disease. A potential novel T. annulata haplotype based on the Tam-1 gene was identified with accession numbers OR364144 and OR915851. Therefore, T. annulata was the only Theileria species found and played a significant problem in the cattle population. This study could be the basis for future studies on unexplored regions and different animal species for well-structured prevention and control measures.

Health Disparities in Cardiac Critical Care: Understanding Inequities, Barriers, and Pathways Toward Equitable Access and Enhanced Outcomes.

Health disparities in cardiac critical care continue to pose significant challenges in achieving equitable access and outcomes for diverse populations. This literature review examines the disparities in access to and outcomes of cardiac critical care interventions across different populations, identifies barriers contributing to these disparities, and explores strategies to address them. A literature review was conducted by searching electronic databases for relevant articles published between January 2000 and May 2023. Studies focusing on health disparities in cardiac critical care, access to interventions, outcomes, and equity were included. Data were extracted and synthesized using a narrative approach. Disparities in access to cardiac critical care interventions were identified, including socioeconomic factors, lack of health insurance, geographic barriers, racial and ethnic disparities, language and cultural barriers, limited health literacy, and lack of awareness and education. These barriers led to delayed diagnoses, suboptimal utilization of interventions, and limited access to specialized cardiac care. Disparities in outcomes were also observed, with certain populations experiencing worse clinical outcomes and higher morbidity and mortality rates. This review emphasizes the existence of disparities in cardiac critical care and emphasizes the necessity for interventions to address these disparities. Specific strategies should concentrate on enhancing healthcare access, diminishing financial obstacles, expanding health insurance coverage, fostering patient-centered approaches, and harnessing telemedicine and technology. Collaborative efforts among policymakers, healthcare providers, researchers, and patient advocates are vital to advocate for policy changes and implement evidence-based interventions that foster equitable care. Future research should prioritize longitudinal studies, implementation science, patient engagement, global perspectives, and rigorous evaluation of intervention strategies to advance our knowledge and guide endeavors in reducing health disparities in cardiac critical care.

Unleashing synergistic co-sensitization of BOA dyes and Ru(ii) complexes for dye-sensitized solar cells: achieving remarkable efficiency exceeding 10% through comprehensive characterization, advanced modeling, and performance analysis.

Dye-sensitized solar cells (DSSCs) have emerged as a promising alternative for renewable energy conversion. The synthesis and characterization of the 2-acetonitrile-benzoxazole (BOA) sensitizer MSW-1-4 are presented along with their chemical structures. Four new organic dyes, MSW-1 through MSW-4, were synthesized using BOA as the main building block, with different additional donor groups. The dyes were characterized and their photophysical and electrochemical properties were studied. Computational modeling using density functional theory (DFT) was performed to investigate their potential as sensitizers/co-sensitizers for photovoltaic applications. The modeling showed a distinct charge separation between the donor and acceptor parts of the molecules. For dye-sensitized solar cells, MSW-4 performed the best out of MSW-1-3 and was also better than the reference dye D-5. Moreover, MSW-3 was co-sensitized along with a typical highly efficient bipyridyl Ru(ii) sensitizer, N719, reference dye D-5, and metal-free dye MSW-4, to induce light harvesting over the expanded spectral region and hence improve the efficiency. Co-sensitizer (MSW-3 + N719) showed an improved efficiency of 10.20%. This outperformed a solar cell that used only N719 as the sensitizer, which had an efficiency of 7.50%. The appropriate combined dye loading of MSW-3 + N719 enabled good light harvesting and maximized the photoexcitation. The synergistic effect of using both MSW-3 and N719 as co-sensitizers led to enhanced solar cell performance compared with using N719 alone.

Revision after prior failed pectus excavatum repair: higher risks and greater complications than primary surgery.

Background: Revision of a prior failed pectus excavatum (PE) repair is occasionally required. These procedures may be technically more complex and have a greater risk of complications. This study was performed to evaluate the outcomes of adult patients undergoing revision procedures. Methods: A retrospective review of adult patients who underwent revision of a prior PE repair from 2010 to 2023 at Mayo Clinic Arizona was performed. Patients were classified by prior procedure [minimally invasive repair of pectus excavatum (MIRPE), Open/Ravitch, and both] and the type of revision procedure performed [MIRPE, hybrid MIRPE, complex hybrid reconstruction, or complex reconstruction of acquired thoracic dystrophy (ATD)]. Outcomes and complications of these groups were analyzed and compared. Results: In total, 190 revision cases were included (mean age was 33±10 years; 72.6% males, mean Haller Index: 4.4±1.8). For the initial repair procedure, 90 (47.4%) patients had a previous MIRPE, 87 (45.8%) patients a prior open repair, and thirteen (6.8%) patients had both. Furthermore, 30 (15.8%) patients had two or more prior interventions. Patients having had a prior MIRPE were able to be repaired with a revision MIRPE in 82.2% of the cases. Conversely, patients with a prior open repair (including those who had both prior MIRPE and open repairs) were much more likely to require complex reconstructions (85%) as none of the ATD patients in this group had an attempted MIRPE. Operative times were shortest in the MIRPE redo approach and longest in the complex reconstruction of the ATD patients (MIRPE 3.5±1.3 hours, ATD 6.9±1.8 hours; P<0.001). The median length of hospital stay was 5 days [interquartile range (IQR), 3.0 days] with the shortest being the MIRPE approach and the longest occurring in the complex reconstruction of the ATD patients [MIRPE 4 days (IQR, 3.0 days); ATD 7 days (IQR, 4.0 days); P<0.001]. Major and minor complications were more frequent in the ATD complex reconstruction group. Preoperative chronic pain was present in over half of the patients (52.6%). Although resolution was seen in a significant number of patients, significant pain issues persisted in 8.8% of the patients postoperatively. Overall, persistent, long term chronic pain was greatest in the post open/Ravitch patient group (open 13.6% vs. MIRPE 3.6%, P=0.02). Conclusions: Revision of a prior failed PE repair can be technically complex with a high risk of complications, prolonged duration of surgery, and lengthy hospitalization. Chronic pain is prevalent and its failure to completely resolve after surgery is not uncommon. The initial failed repair will influence the type of procedure that can be performed and potentially subsequent complications. Even when some recurrences after previous PE surgeries can be repaired with acceptable results, this study demonstrates the importance of proper primary repair due to these increased risks.

Modulating the HSP90 control over NFκB/NLRP3/Caspase-1 axis is a new therapeutic target in the management of liver fibrosis: Insights into the role of TAS-116 (Pimitespib).

Aberrant activation of the NLRP3 inflammasome is recognized to induce a chronic inflammatory response in the liver, ultimately leading to hepatic fibrosis. HSP90 is suggested to regulate NLRP3 activation and its downstream signaling. This study is the first to explore the potential therapeutic role of pimitespib in mitigating liver fibrosis in rats. The results of the study revealed that pimitespib effectively suppressed hepatic inflammation and fibrogenesis by modulating HSP90's control over the NFκB/NLRP3/caspase-1 axis. In vitro experiments demonstrated that pimitespib reduced LDH levels and increased hepatocyte survival, whereas in vivo, it prolonged the survival of rats with hepatic fibrosis. Additionally, pimitespib exhibited improvements in the function and microscopic characteristics of rat livers. Pimitespib effectively inhibited NFκB, which serves as the priming signal for NLRP3 activation. Pimitespib's inhibitory effect on NLRP3, identified as an HSP90 client protein, plays a central role in the observed anti-fibrotic effect. The simultaneous inhibition of both priming and activation signals of NLRP3 by pimitespib led to a reduction in caspase-1 activity and subsequent suppression of the N-terminal fragment of gasdermin D, ultimately constraining hepatocyte pyroptotic cell death. These diverse effects were associated with a decrease in the transcription of inflammatory mediators IL-1ß, IL-18, and TNF-α, as well as the fibrogenic mediators TGF-ß, TIMP-1, PDGF-BB, and Col1a1. Moreover, pimitespib induced the expression of HSP70, which could further contribute to the repression of fibrosis development. In summary, our findings provide an evolutionary perspective on managing liver fibrosis, positioning pimitespib as a promising candidate for anti-inflammatory and antifibrotic therapy.

NAD+ and Niacin Supplementation as Possible Treatments for Glaucoma and Age-Related Macular Degeneration: A Narrative Review.

Glaucoma and age-related macular degeneration (AMD) are progressive retinal diseases characterized by increased oxidative stress, inflammation, and mitochondrial dysfunction. This review investigates the potential therapeutic benefits of NAD+ and niacin supplementation in managing glaucoma and AMD. A literature search was conducted encompassing keywords such as "niacin", "NAD", "glaucoma", "AMD", and "therapeutics". NAD+ depletion is associated with increased oxidative stress and mitochondrial dysfunction in glaucoma and AMD. Niacin, a precursor to NAD+, has shown promise in replenishing NAD+ levels, improving choroidal blood flow, and reducing oxidative damage. Animal studies in glaucoma models indicate that nicotinamide (NAM) supplementation preserves RGC density and function. Large-scale population-based studies indicate an inverse correlation between niacin intake and glaucoma prevalence, suggesting a preventative role. Randomized controlled trials assessing niacin supplementation showed significant improvements in visual field sensitivity and inner retinal function, with a dose-dependent relationship. In AMD, nicotinamide supplementation may improve rod cell function and protect against oxidative stress-induced damage. Cross-sectional studies reveal that individuals with AMD have a lower dietary intake of niacin. Further studies suggest niacin's role in improving choroidal blood flow and dilating retinal arterioles, potentially mitigating ischemic damage and oxidative stress in AMD. Beyond current management strategies, NAD+ and niacin supplementation may offer novel therapeutic avenues for glaucoma and AMD. Further research is warranted to elucidate their efficacy and safety in clinical settings.

Diversity gaps among practicing ophthalmologists in Canada: a landscape study.

OBJECTIVE: Outline geographic disparities in access to language-and gender-concordant ophthalmologic care in Canada. DESIGN: Cross-sectional. PARTICIPANTS: Practicing ophthalmologists in Canada (September 2023). METHODS: Data on ophthalmologists, including demographics, languages spoken, and practice locations, were collected from provincial regulatory body websites. Population data were extracted from the 2021 Statistics Canada Census. Ratio of ophthalmologists-to-potential patients and mean distances (absolute, population-weighted) to gender- and language-concordant care were calculated. The five most common languages spoken in the included provinces were analyzed. RESULTS: There were 986 and 1338 ophthalmologists in the language and gender analysis, respectively. Few ophthalmologists spoke non-official languages in Saskatchewan, Manitoba, and Nova Scotia. In a population-weighted analysis, the distance to a language-concordant ophthalmologist were 4.55 times greater for Spanish speakers compared to their English counterparts. Cantonese speakers had the shortest distances to language-concordant care but were still had 40% greater distance than English speakers in the same regions. Despite French-speaking ophthalmologists being the most prevalent per 100 000 speakers, francophones outside Quebec endured distances over double that of anglophones to access language-concordant care. Females in Newfoundland and Saskatchewan faced the longest distances to access gender-concordant care. In Ontario, females may face 3 times the distance to gender-concordant ophthalmologists compared to males. Quebec approaches gender parity with a male-to-female ratio of 55:45. CONCLUSIONS: The results highlight the disparities in accessibility to non-English ophthalmologic care and the underrepresentation of female ophthalmologists across Canada. These disparities underscore the need for targeted strategies to ensure that the ophthalmologic workforce mirrors the demographic of the population it serves.

Characterization and application of LDH with chitosan composites investigated by positron annihilation lifetime spectroscopy and surface texture for the adsorption of methyl orange.

With a rapid increase in industrial growth around the world, the demand for an entirely novel category of nanoparticles and technologies for wastewater treatment has become a key concern for environmental protection. Recently, hybrids of layered double hydroxides (LDH), particularly those containing LDH, have gained attention as potential nanoscale adsorbents for water treatment. Recent research has shown that LDH-containing composites are interesting versatile materials with the ability to be used in energy storage, photocatalysis, nanocomposites, and water treatment. In the current work, LDH-containing composites were utilized as adsorbents for the purpose of purifying water. The adsorbents investigated are Zn-Co-Fe/LDH/Chitosan-in situ sample preparation (LDH/CS1) and Zn-Co-Fe/LDH/Chitosan-ex situ sample preparation (LDH/CS2). Furthermore, LDH/CS1 and LDH/CS2 were investigated for wastewater treatment from methyl orange dye (MO) with various adsorption conditions. When the initial MO concentration was 20 mg/L and the amount of adsorbent was 0.1 g, the removal efficiency reached 72.8 and 91.7% for LDH/CS1 and LDH/CS2, respectively. The MO's maximum adsorption capabilities are 160.78 and 165.89 mg/g for LDH/CS1 and LDH/CS2, respectively, which is much greater than that of comparable commercial adsorbents. MO adsorption onto LDH/CS1 and LDH/CS2 was best characterized by the pseudo-second-order kinetic model. The equilibrium adsorption data was followed by the Freundlich and Langmuir models. The adsorption is favorable as evidenced by the equilibrium parameter RL values for MO adsorption onto LDH/CS1 and LDH/CS2, which were 0.227 and 0.144, respectively. Using the free volume distribution method and the positron annihilation lifetime technique, the nanostructure of the materials was examined.

Unveiling the influence of salinity on bacterial microbiome assembly of halophytes and crops.

BACKGROUND: Climate change and anthropogenic activities intensify salinity stress impacting significantly on plant productivity and biodiversity in agroecosystems. There are naturally salt-tolerant plants (halophytes) that can grow and withstand such harsh conditions. Halophytes have evolved along with their associated microbiota to adapt to hypersaline environments. Identifying shared microbial taxa between halophyte species has rarely been investigated. We performed a comprehensive meta-analysis using the published bacterial 16S rRNA gene sequence datasets to untangle the rhizosphere microbiota structure of two halophyte groups and non-halophytes. We aimed for the identification of marker taxa of plants being adapted to a high salinity using three independent approaches. RESULTS: Fifteen studies met the selection criteria for downstream analysis, consisting of 40 plants representing diverse halophyte and non-halophyte species. Microbiome structural analysis revealed distinct compositions for halophytes that face high salt concentrations in their rhizosphere compared to halophytes grown at low salt concentrations or from non-halophytes. For halophytes grown at high salt concentrations, we discovered three bacterial genera that were independently detected through the analysis of the core microbiome, key hub taxa by network analysis and random forest analysis. These genera were Thalassospira, Erythrobacter, and Marinobacter. CONCLUSIONS: Our meta-analysis revealed that salinity level is a critical factor in affecting the rhizosphere microbiome assembly of plants. Detecting marker taxa across high-halophytes may help to select Bacteria that might improve the salt tolerance of non-halophytic plants.

The Satisfaction and Quality of Life of Patients After Breast Reconstruction: A Cross-Sectional Multicenter Study Comparing Immediate, Delayed, and Nonreconstructive Outcomes.

BACKGROUND: Breast reconstruction following mastectomy can be performed through various surgical techniques that prioritize the patient's safety and quality of life. Plastic surgeons are trained to choose the most appropriate surgical approach based on the individual patient's needs and medical history. The safety of the patient is always the primary concern, followed by considerations such as aesthetic outcomes and long-term health implications. OBJECTIVES: The aim of this study was to assess and document patients' satisfaction and quality of life after breast reconstruction across Saudi Arabia. METHODS: This is a cross-sectional multicenter study among female patients who underwent mastectomy with or without breast reconstruction between 2015 and 2022. Two hundred eighty patients participated in this study through a call-based Arabic version of the BREAST-Q questionnaire to analyze the quality of their lives and satisfaction. RESULTS: Our results showed that patients who underwent delayed reconstruction had lower satisfaction than those who underwent immediate reconstruction. The average BREAST-Q score was lower in patients who used tissue expanders than those with implant-based reconstruction, autologous reconstruction, or combined approaches. Patients who underwent simple mastectomy had lower satisfaction (M = 66.1) than those who had a skin-sparing mastectomy (M = 71.1) and/or nipple-sparing mastectomy (M = 72.6). CONCLUSIONS: This retrospective multicenter study observed a significant association between the time of the reconstructive surgery and patient's satisfaction; patients who underwent immediate reconstruction had higher satisfaction rate. Lower satisfaction rate was associated with tissue expander breast reconstruction. There is a significant association between satisfaction rate and smoking history.

Hyperkinetic Biliary Dyskinesia: An Underrecognized Problem With Good Surgical Outcomes After Cholecystectomy.

Introduction While surgical indications for symptomatic cholelithiasis and biliary hypokinesia are clear, hyperkinetic biliary dyskinesia (HBD) is an underrecognized condition with poorly defined symptomology and management guidelines. HBD is typically defined as a gallbladder ejection fraction (EF) ≥ 80% on a hepatobiliary iminodiacetic acid (HIDA) scan. We aimed to identify the prevalence and radiographic reporting of HBD, physician referral patterns, and clinical outcomes following cholecystectomy. Methods  A retrospective cohort study of patients with HIDA scans completed over 21 years at our tertiary care hospital was performed. Demographics, symptomatology, referral patterns, and operative data were collected. HBD was defined as HIDA EF ≥80%. Patients with HBD who underwent cholecystectomy were analyzed. ANOVA and chi-square tests were used to compare variables among patients with or without symptom improvement using Statistical Product and Service Solutions (SPSS; IBM SPSS Statistics for Windows, Armonk, NY). Results Of 1,997 patients (73% female, mean age 51.7 years) who had HIDA scans with reported EF, 730 (36.6%) had an EF≥80%. Only 13.7% of HIDA scans with EF≥80% were reported as hyperkinetic, and the rest are "normal". Cholecystectomy was performed in 57 (7.8%) patients with EF≥80%, most being elective (89.5%) and all minimally invasive. Primary care physicians (PCPs) referred most elective cases to surgery (61.4%). The median time from HIDA to cholecystectomy was 146 days. Chronic cholecystitis was common in pathology (82.5%), while 38.6% had cholelithiasis. Overall, 53 patients (93.0%) reported symptom improvement at a median follow-up of 17.0 days. Patients without improvement had a higher prevalence of chronic gastrointestinal conditions (p<0.05), but not significantly more cholelithiasis, cholecystitis, time to surgery, or elective surgery status. Conclusions HBD is common but often underdiagnosed and thus likely underrecognized by treating physicians. Most HBD patients benefit from cholecystectomy, regardless of cholelithiasis. Patients with persistent symptoms after cholecystectomy may have confounding gastrointestinal diagnoses. Increased awareness among radiologists, referring PCPs, gastroenterologists, and surgeons about HBD and postoperative outcomes is needed to ensure that HBD is adequately treated.

Gemcitabine and synthesized silver nanoparticles impact on chemically induced hepatocellular carcinoma in male rats.

Objective: Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used to treat many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used to treat many diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method. This study aims to evaluate the efficiency of co-treating gemcitabine and silver nanoparticles in treating hepatocellular carcinoma. Method: The AgNPs were characterized using UV-visible spectroscopy, XRD, TEM, and EDX. The MTT cytotoxicity in vitro assay of gemcitabine, doxorubicin, and cyclophosphamide was assessed against Wi38 normal fibroblast and HepG2 HCC cell lines. After HCC development, rats received (10 µg/g b.wt.) of AgNPs three times a week for 4 weeks and/or GEM (5 mg/kg b.wt.) twice weekly for 4 weeks. Liver function enzymes were investigated. Cytochrome P450 and miR-21 genes were studied. Apoptosis was determined by using flow cytometry, and apoptotic modifications in signaling pathways were evaluated via Bcl-2, Bax, Caspase-9, and SMAD-4. Results: The co-treatment of GEM and AgNPs increased apoptosis by upregulating Bax and caspase 9 while diminishing Bcl2 and SMAD4. It also improved cytochrome P450 m-RNA relative expression. The results also proved the cooperation between GEM and AgNPs in deactivating miR21. The impact of AgNPs as an adjuvant treatment with GEM was recognized. Conclusions: The study showed that co-treating AgNPs and GEM can improve the efficiency of GEM alone in treating HCC. This is achieved by enhancing intrinsic and extrinsic apoptotic pathways while diminishing some drawbacks of using GEM alone.

How does a Saccharomyces cerevisiae extract influence the components of isolated rotavirus particles from stool samples collected in a clinical setting from children?

Human Rotavirus (HRV) is the causative pathogen of severe acute enteric infections that cause mortality among children worldwide. This study focuses on developing a new and effective treatment for rotavirus infection using an extract from Saccharomyces cerevisiae, aiming to make this treatment easily accessible to everyone. 15 antigens and 26 antibodies were detected in serum and stool using ELISA. The titers of HRVq1, HRVq2, HRVC1, and HRVC2 on Vero cells were determined to be 1.2x106, 3.0x106, 4.2x106, and 7.5x105 (Plaque forming unit, PFU/ml) four days after infection, respectively. The HRVq1 isolate induced cytopathic effects, i.e., forming multinucleated, rounded, enlarged, and expanding gigantic cells. RT-PCR identified this isolate, and the accession number 2691714 was assigned to GeneBank. The molecular docking analysis revealed that nonstructural proteins (NSPs) NSP1, NSP2, NSP3, NSP4, NSP5, and NSP6 exhibited significant binding with RNA. NSP2 demonstrated the highest binding affinity and the lowest binding energy (-8.9 kcal/mol). This affinity was maintained via hydrophobic interactions and hydrogen bonds spanning in length from 1.12 Å to 3.11 Å. The ADMET and bioactivity predictions indicated that the yeast extract possessed ideal solubility, was nontoxic, and did not cause cancer. The inhibitory constant values predicted for the S. cerevisiae extract in the presence of HRV vital proteins varied from 5.32 to 7.45 mM, indicating its potential as a viable drug candidate. Saccharomyces cerevisiae extract could be utilized as a dietary supplement to combat HRV as an alternative dietary supplement.

Morphomolecular identification of heavy parasitic typhlitis in layer flocks: tissue response and cell-mediated reaction.

BACKGROUND: Heterakis gallinarum (H. gallinarum) is a common poultry parasite that can be found in the ceca of many gallinaceous bird species, causing minor pathology and reduced weight gain. Most infections go unnoticed in commercial flocks due to the dependence on fecal egg counts, which are prone to false-negative diagnoses. Furthermore, there is a lack of research on gastrointestinal nematodes that use molecular identification methods, which could be essential for rapid diagnosis and developing efficient control approaches. As a result, the study aimed to look at the cause of mortality in layer chickens induced by H. gallinarum in Egyptian poultry farms using morphological, ultrastructural, and molecular characterization. Histopathological, immunohistochemical, and cell-mediated immune responses from damaged cecal tissues were also examined. RESULTS: Seventy bird samples from ten-layer flocks of different breeds (Native, white, and brown layers) suffering from diarrhea, decreased egg output, and emaciation were collected. Cecal samples were collected from affected and non-affected birds and were examined for parasitic diseases using light and a scanning electron microscope. The mitochondrial cytochrome oxidase 1 (COX1) gene was used to characterize H. gallinarum. Our results showed that the collected nematodal worms were identified as H. gallinarum (male and female), further confirmed by COX1 gene amplification and sequence alignment. Gene expression analysis of the inflammatory markers in infected tissues showed a significant up-regulation of IL-2, IFN-γ, TLR-4, and IL-1ß and a significant down-regulation of the anti-inflammatory IL-10. The mRNA level of the apoptotic cas-3 revealed apoptotic activity among the H. gallinarum samples compared to the control group. CONCLUSIONS: Our results implemented the use of molecular methods for the diagnosis of Heterakis, and this is the first report showing the tissue immune response following infection in layers: upregulation of IL-1ß, IFN-γ, Il-2, and TLR-4, while down-regulation of anti-inflammatory IL-10 in cecal tissue, Cas-3 apoptotic activity and Nuclear factor-κB (NF-κB)activity with immunophenotyping of T-cells in Heterakis infected tissue.

Development of non-acidic 4-methylbenzenesulfonate-based aldose reductase inhibitors; Design, Synthesis, Biological evaluation and in-silicostudies.

Design and virtual screening of a set of non-acidic 4-methyl-4-phenyl-benzenesulfonate-based aldose reductase 2 inhibitors had been developed followed by chemical synthesis. Based on the results, the synthesized compounds 2, 4a,b, 7a-c, 9a-c, 10a-c, 11b,c and 14a-c inhibited the ALR2 enzymatic activity in a submicromolar range (99.29-417 nM) and among them, the derivatives 2, 9b, 10a and 14b were able to inhibit ALR2 by IC50 of 160.40, 165.20, 99.29 and 120.6 nM, respectively. Moreover, kinetic analyses using Lineweaver-Burk plot revealed that the most active candidate 10a inhibited ALR2 potently via a non-competitive mechanism. In vivo studies showed that 10 mg/kg of compound 10a significantly lowered blood glucose levels in alloxan-induced diabetic mice by 46.10 %. Moreover, compound 10a showed no toxicity up to a concentration of 50 mg/kg and had no adverse effects on liver and kidney functions. It significantly increased levels of GSH and SOD while decreasing MDA levels, thereby mitigating oxidative stress associated with diabetes and potentially attenuating diabetic complications. Furthermore, the binding mode of compound 10a was confirmed through MD simulation. Noteworthy, compounds 2 and 14b showed moderate antimicrobial activity against the two fungi Aspergillus fumigatus and Aspergillus niger. Finally, we report the thiazole derivative 10a as a new promising non-acidic aldose reductase inhibitor that may be beneficial in treating diabetic complications.

Bariatric Surgery Is Associated with Lower Concentrations of Fecal Secondary Bile Acids and Their Metabolizing Microbial Enzymes: A Pilot Study.

INTRODUCTION: Excess body fat elevates colorectal cancer risk. While bariatric surgery (BRS) induces significant weight loss, its effects on the fecal stream and colon biology are poorly understood. Specifically, limited data exist on the impact of bariatric surgery (BRS) on fecal secondary bile acids (BA), including lithocholic acid (LCA), a putative promotor of colorectal carcinogenesis. METHODS: This cross-sectional case-control study included 44 patients with obesity; 15 pre-BRS (controls) vs. 29 at a median of 24.1 months post-BRS. We examined the fecal concentrations of 11 BA by liquid chromatography and gene abundance of BA-metabolizing bacterial enzymes through fecal metagenomic sequencing. Differences were quantified using non-parametric tests for BA levels and linear discriminant analysis (LDA) effect size (LEfSe) for genes encoding BA-metabolizing enzymes. RESULTS: Total fecal secondary BA concentrations trended towards lower levels post- vs. pre-BRS controls (p = 0.07). Individually, fecal LCA concentrations were significantly lower post- vs. pre-BRS (8477.0 vs. 11,914.0 uM/mg, p < 0.008). Consistent with this finding, fecal bacterial genes encoding BA-metabolizing enzymes, specifically 3-betahydroxycholanate-3-dehydrogenase (EC 1.1.1.391) and 3-alpha-hydroxycholanate dehydrogenase (EC 1.1.1.52), were also lower post- vs. pre-BRS controls (LDA of - 3.32 and - 2.64, respectively, adjusted p < 0.0001). Post-BRS fecal BA concentrations showed significant inverse correlations with weight loss, a healthy diet quality, and increased physical activity. CONCLUSIONS: Concentrations of LCA, a secondary BA, and bacterial genes needed for BA metabolism are lower post-BRS. These changes can impact health and modulate the colorectal cancer cascade. Further research is warranted to examine how surgical alterations and the associated dietary changes impact bile acid metabolism.